Dipartimento di Scienze della Salute, Università degli Studi di Milano, Ospedale San Paolo, Via Antonio di Rudinì 8, 20142 Milan, Italy.
IRCCS Multimedica, Servizio Statistico, 20138 Milan, Italy.
Int J Mol Sci. 2019 Jul 25;20(15):3646. doi: 10.3390/ijms20153646.
Episodes of hypoglycemia are frequent in patients with diabetes treated with insulin or sulphonylureas. Hypoglycemia can lead to severe acute complications, and, as such, both prevention and treatment of hypoglycemia are important for the well-being of patients with diabetes. The experience of hypoglycemia also leads to fear of hypoglycemia, that in turn can limit optimal glycemic control in patients, especially with type 1 diabetes. Treatment of hypoglycemia is still based on administration of carbohydrates (oral or parenteral according to the level of consciousness) or of glucagon (intramuscular or subcutaneous injection). In 1983, it was shown for the first time that intranasal (IN) glucagon drops (with sodium glycocholate as a promoter) increase blood glucose levels in healthy volunteers. During the following decade, several authors showed the efficacy of IN glucagon (drops, powders, and sprays) to resolve hypoglycemia in normal volunteers and in patients with diabetes, both adults and children. Only in 2010, based on evaluation of patients' beliefs and patients' expectations, a canadian pharmaceutical company (Locemia Solutions, Montreal, Canada) reinitiated efforts to develop glucagon for IN administration. The project has been continued by Eli Lilly, that is seeking to obtain registration in order to make IN glucagon available to insulin users (children and adolescents) worldwide. IN glucagon is as effective as injectable glucagon, and devoid of most of the technical difficulties associated with administration of injectable glucagon. IN glucagon appears to represent a major breakthrough in the treatment of severe hypoglycemia in insulin-treated patients with diabetes, both children and adults.
接受胰岛素或磺酰脲类药物治疗的糖尿病患者常发生低血糖事件。低血糖可导致严重的急性并发症,因此预防和治疗低血糖对糖尿病患者的健康都非常重要。低血糖发作的经历也会导致患者对低血糖的恐惧,这反过来又会限制患者(尤其是 1 型糖尿病患者)的血糖控制达到最佳水平。低血糖的治疗仍然基于给予碳水化合物(根据意识水平给予口服或胃肠外)或给予胰高血糖素(肌肉内或皮下注射)。1983 年,首次证明经鼻(IN)给予胰高血糖素滴剂(以甘胆酸钠作为促进剂)可使健康志愿者的血糖水平升高。在随后的十年中,几位作者证明了 IN 胰高血糖素(滴剂、粉剂和喷雾剂)在正常志愿者和糖尿病患者(包括成人和儿童)中用于解决低血糖的疗效。直到 2010 年,基于对患者信念和患者期望的评估,一家加拿大制药公司(Locemia Solutions,加拿大蒙特利尔)重新开始努力开发 IN 给药用胰高血糖素。该项目由礼来公司继续进行,旨在获得注册,以便使全球的胰岛素使用者(儿童和青少年)都能获得 IN 胰高血糖素。IN 胰高血糖素与注射用胰高血糖素同样有效,且几乎没有与注射用胰高血糖素给药相关的大多数技术难题。IN 胰高血糖素似乎代表了在治疗接受胰岛素治疗的糖尿病患者(包括儿童和成人)严重低血糖方面的重大突破。